Insulin sensitivity following Agent Orange exposure in Vietnam veterans with high blood levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin

Our objective was to determine whether insulin sensitivity was related to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Vietnam veterans exposed to Agent Orange. Air Force veterans of Operation Ranch Hand, the unit responsible for spraying Agent Orange and other herbicides in Vietnam from 1962 to 1971, and comparison veterans who did not spray herbicides were included. We measured insulin sensitivity (S_I) using a frequently sampled iv glucose tolerance test in a matched study of 29 matched pairs of veterans and a quantitative insulin sensitivity check index (QUICKI) based on fasting glucose and insulin in 71 matched pairs. No group differences were found with regard to the mean values of S_I, QUICKI, TNFα, adiponectin, and two measures of insulin secretion. However, S_I and QUICKI decreased significantly with regard to TCDD (P = 0.01 and 0.02). A corresponding pattern (although not significant) was found for blood levels of TNFα and adiponectin. These data suggest that high blood TCDD levels may promote an insulin-resistant state, but the magnitude of this effect appeared to be small, such that an 18-fold increase in blood TCDD due to increased exposure resulted in only a 10% change in S_I in the 29 matched pairs.